The sound of tumor cell-microenvironment communication – composed by the Cancer Cluster Salzburg research network

Weßler, Silja; Aberger, Fritz; Hartmann, Tanja Nicole

doi:10.1186/s12964-017-0176-z

Cited by 11 publications

(7 citation statements)

References 11 publications

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“…It is well known that the TME mediates immune escape and regulates the sensitivity of tumors to anticancer drugs. The TME is composed of various types of immune cells, including T cells, NK cells and dendritic cells, which are responsible for anticancer immunity ( 51 ). Regulatory T cells (Tregs) have immunosuppressive effects because they can promote evasion of the recognition of tumor antigens by antigen-presenting cells and T cells ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

IGFBP7 and the Tumor Immune Landscape: A Novel Target for Immunotherapy in Bladder Cancer

Zheng

et al. 2022

Front. Immunol.

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Insulin-like growth factor binding protein-7 (IGFBP7) was recently reported to be a ligand of CD93, a potential target to normalize vasculature and attenuate immunotherapy. However, its role in the tumor microenvironment (TME) and immunotherapy response of bladder cancer (BLCA) remains unclear. We comprehensively evaluated the correlation between IGFBP7 and multiple immunological characteristics of BLCA across The Cancer Genome Atlas (TCGA) and two external cohorts. Importantly, the response of IGFBP7-grouped BLCA patients to immunotherapy was predicted and validated by five real-word immunotherapy cohorts. Finally, we developed an IGFBP7-based immune risk model validated by five independent cohorts. IGFBP7 modulated the TME across pan-caners. In BLCA, high expression of IGFBP7 was correlated with more aggressive clinical features. IGFBP7 was positively associated with immunomodulators and promoted tumor-infiltrating lymphocyte trafficking into the tumor microenvironment. However, T cells recognition and tumor cell killing were lower in the high-IGFBP7 group. In addition, high expression of IGFBP7 displayed lower enrichment scores for most pro-immunotherapy pathways. Clinical data from IMvigor210 and GSE176307 indicated that IGFBP7 negatively correlated with the BLCA immunotherapy response. The same trend was also observed in a renal cell carcinoma (RCC) cohort and two melanoma cohorts. Notably, urothelial and luminal differentiation were less frequently observed in the high-IGFBP7 group, while neuroendocrine differentiation was more frequently observed. Mechanistically, high IGFBP7 was associated with an enriched hypoxia pathway and higher expression of key genes in ERBB therapy and antiangiogenic therapy. Furthermore, our IGFBP7-based immune risk model was able to predict the prognosis and response to immunotherapy with good accuracy (5-year AUC = 0.734). Overall, IGFBP7 plays a critical role in the immunoregulation and TME of BLCA and may serve as a novel potential target for combination treatment with immunotherapy for BLCA.

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Section: Discussionmentioning

confidence: 99%

IGFBP7 and the Tumor Immune Landscape: A Novel Target for Immunotherapy in Bladder Cancer

Zheng

et al. 2022

Front. Immunol.

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“…PC substrates also mediate the interaction between tumour cells and the immune system and mark the boundary difference between the immune-vigilance and immune-escape of the tumour [ 81 ]. In this context, the suppression of PCs has been shown to lower T cell exhaustion and immune escape, making them interesting targets for immunotherapy [ 106 ]. Some pro-inflammatory PC substrates are found in the tumour necrosis factor superfamily: TNF-α, TWEAK, TGF-β, B-cell activating factor, APRIL, several chemokines and hepcidin [ 81 ].…”

Section: Cancer and Inflammationmentioning

confidence: 99%

Testicular Germ Cell Tumours and Proprotein Convertases

Velado-Eguskiza

Gomez-Santos

Badiola

et al. 2022

Cancers

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Testicular Germ Cell Tumours (TGCT) are widely considered a “curable cancer” due to their exceptionally high survival rate, even if it is reduced by many years after the diagnosis due to metastases and relapses. The most common therapeutic approach to TGCTs has not changed in the last 50 years despite its multiple long-term side effects, and because it is the most common malignancy in young Caucasian men, much research is needed to better the quality of life of the many survivors. Proprotein Convertases (PC) are nine serine proteases responsible for the maturation of inactive proproteins with many diverse functions. Alterations in their expression have been associated with various diseases, including cancer and inflammation. Many of their substrates are adhesion molecules, metalloproteases and proinflammatory molecules, all of which are involved in tumour development. Inhibition of certain convertases has also been shown to slow tumour formation, demonstrating their involvement in this process. Considering the very established link between PCs and inflammation-related malignancies and the recent studies carried out into the immune microenvironment of TGCTs, the study of the involvement of PCs in testicular cancer may open up avenues for being both a biomarker for diagnosis and a therapeutic target.

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“…In the tumor microenvironment, intercellular communication (e.g., cross-talk between cancer cell and stromal cells) plays key roles in promoting tumor progression and metastasis [61]. Cancer cells secrete more exosomes than healthy cells [62].…”

Section: Exosomes In the Livermentioning

confidence: 99%

Liver-Derived Exosomes and Their Implications in Liver Pathobiology

Sung

Kim

Jung

2018

IJMS

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The liver has a wide range of physiological functions in the body, and its health is maintained by complex cross-talk among hepatic cells, including parenchymal hepatocytes and nonparenchymal cells. Exosomes, which are one method of cellular communication, are endosomal-derived small vesicles that are released by donor cells and delivered to the target cells at both short and long distances. Because exosomes carry a variety of cargoes, including proteins, mRNAs, microRNAs and other noncoding RNAs originating from donor cells, exosomes convey cellular information that enables them to potentially serve as biomarkers and therapeutics in liver diseases. Hepatocytes release exosomes to neighboring hepatocytes or nonparenchymal cells to regulate liver regeneration and repair. Nonparenchymal cells, including hepatic stellate cells, liver sinusoidal endothelial cells, and cholangiocytes, also secrete exosomes to regulate liver remodeling upon liver injury. Exosomes that are released from liver cancer cells create a favorable microenvironment for cancer growth and progression. In this review, we summarize and discuss the current findings and understanding of exosome-mediated intercellular communication in the liver, with a particular focus on the function of exosomes in both health and disease. Based on the current findings, we suggest the potential applications of exosomes as biomarkers and therapeutics for liver diseases.

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The sound of tumor cell-microenvironment communication – composed by the Cancer Cluster Salzburg research network

Cited by 11 publications

References 11 publications

IGFBP7 and the Tumor Immune Landscape: A Novel Target for Immunotherapy in Bladder Cancer

IGFBP7 and the Tumor Immune Landscape: A Novel Target for Immunotherapy in Bladder Cancer

Testicular Germ Cell Tumours and Proprotein Convertases

Liver-Derived Exosomes and Their Implications in Liver Pathobiology

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